CA2667957A1 - Methods and apparatuses for electrochemical determination of factor xa inhibitors in blood samples - Google Patents
Methods and apparatuses for electrochemical determination of factor xa inhibitors in blood samples Download PDFInfo
- Publication number
- CA2667957A1 CA2667957A1 CA002667957A CA2667957A CA2667957A1 CA 2667957 A1 CA2667957 A1 CA 2667957A1 CA 002667957 A CA002667957 A CA 002667957A CA 2667957 A CA2667957 A CA 2667957A CA 2667957 A1 CA2667957 A1 CA 2667957A1
- Authority
- CA
- Canada
- Prior art keywords
- factor
- reagent
- sample
- activator
- test element
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract 10
- 229940123583 Factor Xa inhibitor Drugs 0.000 title claims abstract 8
- 239000008280 blood Substances 0.000 title claims abstract 7
- 210000004369 blood Anatomy 0.000 title claims abstract 7
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract 22
- 108010014173 Factor X Proteins 0.000 claims abstract 21
- GONFBOIJNUKKST-UHFFFAOYSA-N 5-ethylsulfanyl-2h-tetrazole Chemical compound CCSC=1N=NNN=1 GONFBOIJNUKKST-UHFFFAOYSA-N 0.000 claims abstract 13
- 108090000190 Thrombin Proteins 0.000 claims abstract 10
- 229960004072 thrombin Drugs 0.000 claims abstract 10
- 108010074860 Factor Xa Proteins 0.000 claims abstract 9
- 238000001514 detection method Methods 0.000 claims abstract 8
- 239000000126 substance Substances 0.000 claims abstract 6
- 238000006243 chemical reaction Methods 0.000 claims abstract 5
- 239000000758 substrate Substances 0.000 claims abstract 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract 3
- 229920000669 heparin Polymers 0.000 claims abstract 3
- 229940127215 low-molecular weight heparin Drugs 0.000 claims abstract 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 3
- 206010053567 Coagulopathies Diseases 0.000 claims abstract 2
- 230000004913 activation Effects 0.000 claims abstract 2
- 230000035602 clotting Effects 0.000 claims abstract 2
- 230000000694 effects Effects 0.000 claims abstract 2
- 238000002848 electrochemical method Methods 0.000 claims abstract 2
- 229960002897 heparin Drugs 0.000 claims abstract 2
- 230000001404 mediated effect Effects 0.000 claims abstract 2
- 239000012190 activator Substances 0.000 claims 3
- 230000015271 coagulation Effects 0.000 claims 2
- 238000005345 coagulation Methods 0.000 claims 2
- 238000005259 measurement Methods 0.000 claims 2
- 229940123688 Direct Factor Xa inhibitor Drugs 0.000 claims 1
- 108010054265 Factor VIIa Proteins 0.000 claims 1
- 108010071241 Factor XIIa Proteins 0.000 claims 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims 1
- 108010000499 Thromboplastin Proteins 0.000 claims 1
- 102000002262 Thromboplastin Human genes 0.000 claims 1
- 229940019332 direct factor xa inhibitors Drugs 0.000 claims 1
- 238000000840 electrochemical analysis Methods 0.000 claims 1
- 230000006624 extrinsic pathway Effects 0.000 claims 1
- 229940012414 factor viia Drugs 0.000 claims 1
- 230000006623 intrinsic pathway Effects 0.000 claims 1
- 239000003055 low molecular weight heparin Substances 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/001—Enzyme electrodes
- C12Q1/005—Enzyme electrodes involving specific analytes or enzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/56—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/86—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hematology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Neurosurgery (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Electrochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention relates to methods and apparatuses for determining factor Xa inhibitors, especially heparins and fractionated or low molecular weight heparins, and direct FXa inhibitors, in blood samples, which are characterized in that in a first step the blood sample is brought into contact with a detection reagent which comprises at least one thrombin substrate which consists of a peptide residue which can be eliminated by thrombin and which is amidically linked via the carboxyl end to an electrogenic substance, and with a known amount of factor X reagent and an activator reagent which brings about conversion of factor X into factor Xa, subsequently in a second step the amount or activity of the electrogenic substance which is eliminated from the thrombin substrate through the factor Xa-mediated thrombin activation, and/or the time course thereof, is determined as measured signal using electrochemical methods, and finally in a third step, by means of this measured signal, the amount of the factor Xa inhibitor in the sample of the blood to be investigated, or a measured quantity correlating therewith, in particular a clotting time correlating therewith, is ascertained.
Claims (13)
- Claims Method for determining factor Xa inhibitors in blood samples characterized in that a) a sample of the blood to be analysed is brought into contact with a detection reagent which contains at least one thrombin substrate which consists of a peptide residue that can be cleaved by thrombin and which is amidically bound via the carboxyl end to an electrogenic substance, and with a known amount of factor X reagent and an activator reagent which induces the conversion of factor X into factor Xa, b) the amount or activity of the electrogenic substance which is cleaved from the thrombin substrate by the factor Xa-mediated thrombin activation and/or its time course is determined as the measurement signal using electrochemical methods, and c) the amount of the factor Xa inhibitor in the sample of the blood to be analysed or a measured quantity that correlates therewith in particular a clotting time that correlates therewith is determined on the basis of this measurement signal.
- Method according to claim 1, characterized in that an activator or a complex involved in the extrinsic pathway of plasmatic coagulation, in particular tissue factor and/or factor VIIa, or an activator or a complex involved in the intrinsic pathway of plasmatic coagulation in particular factor XIIa or a substance which induces a conversion of factor X
into factor Xa is used as the activator reagent. - 3. Method according to claim 1 or 2, characterized in that the factor X reagent is added to the sample spatially separated from or at a separate time from the addition of the activator reagent to the sample.
- 4. Method according to claim 3, characterized in that the factor X reagent is a component of the detection reagent and this detection reagent / factor X reagent combination is added to the sample spatially separated from or at a separate time from the addition of the activator reagent to the sample and in particular after the activator reagent has been added to the sample.
- 5. Method according to claim 1 or 2, characterized in that factor X is added to the sample in a common step with the addition of the activator to the sample.
- 6. Method according to claim 5, characterized in that the factor X reagent and activator reagent are present together in a dry state and factor X is not converted into factor Xa until contact with the sample.
- 7. Method according to claim 6, characterized in that the factor X reagent, activator reagent and detection reagent are present together in a dry state and factor X is not converted into factor Xa until contact with the sample.
- 8. Method according to one of the previous claims characterized in that the factor Xa inhibitor is a heparin, in particular a fractionated or low-molecular-weight heparin, an indirect selective or a direct factor Xa inhibitor.
- 9. Test element with an electrochemical sensor on a dry chemistry basis for determining factor Xa inhibitors, in particular unfractionated heparins, fractionated or low-molecular-weight heparins, indirect selective factor Xa inhibitors and direct factor Xa inhibitors which, on an inert carrier, has at least two electrodes and a detection reagent which contains at least one thrombin substrate which consists of a peptide residue that can be cleaved by thrombin and is bound amidically via the carboxyl end to an electrogenic substance, as well as at least a certain amount of factor X reagent and an activator reagent.
- 10. Test element according to claim 9, characterized in that the activator reagent is present on the test element at least partially spatially separated from the factor X reagent and is in particular arranged at least partially in front of the factor X reagent in the flow direction of the sample.
- 11. Test element according to claim 10, characterized in that the detection reagent is present on the test element together with the activator reagent or the factor X reagent.
- 12. Test element according to claim 9, characterized in that it contains the factor X reagent and an activator reagent which induces the conversion of factor X into factor Xa as dry chemistry reagents and the activator reagent is present on the test element together with the factor X
reagent and optionally also together with the detection reagent so that the conversion of factor X into factor Xa does not take place until contact with the sample. - 13. Electrochemical test element analytical system, containing at least one device for measuring current or voltage and a test element according to one of the claims 9 to 12.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06123234A EP1918718A1 (en) | 2006-10-31 | 2006-10-31 | Methods and devices for electrochemical determination of factor Xa inhibitors in blood samples |
EP06123234.4 | 2006-10-31 | ||
PCT/EP2007/009347 WO2008052718A1 (en) | 2006-10-31 | 2007-10-27 | Methods and apparatuses for electrochemical determination of factor xa inhibitors in blood samples |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2667957A1 true CA2667957A1 (en) | 2008-05-08 |
CA2667957C CA2667957C (en) | 2013-03-05 |
Family
ID=37633621
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2667957A Expired - Fee Related CA2667957C (en) | 2006-10-31 | 2007-10-27 | Methods and apparatuses for electrochemical determination of factor xa inhibitors in blood samples |
Country Status (8)
Country | Link |
---|---|
US (2) | US8636894B2 (en) |
EP (2) | EP1918718A1 (en) |
JP (1) | JP5395669B2 (en) |
CN (1) | CN101535498B (en) |
CA (1) | CA2667957C (en) |
ES (1) | ES2444011T3 (en) |
HK (1) | HK1137783A1 (en) |
WO (1) | WO2008052718A1 (en) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2471945A1 (en) * | 2010-12-30 | 2012-07-04 | Siemens Healthcare Diagnostics Products GmbH | Method for determining coagulation inhibitors |
JP5946139B2 (en) * | 2011-03-16 | 2016-07-05 | 学校法人 芝浦工業大学 | Anticoagulant measurement sensor |
EP2818871A1 (en) | 2013-06-28 | 2014-12-31 | Roche Diagniostics GmbH | Means and methods for universal calibration of anti-Factor Xa tests |
EP3197603A1 (en) | 2014-09-26 | 2017-08-02 | Abbott Point of Care Inc. | Cartridge device with segmented fluidics for assaying coagulation in fluid samples |
WO2016049557A1 (en) | 2014-09-26 | 2016-03-31 | Abbott Point Of Care Inc. | Ellagic acid formulations for use in coagulation assays |
WO2016049552A1 (en) | 2014-09-26 | 2016-03-31 | Abbott Point Of Care Inc. | Cartridge device identification for coagulation assays in fluid samples |
EP3955003B1 (en) * | 2014-09-26 | 2023-06-21 | Abbott Point Of Care Inc | Sensors for assaying coagulation in fluid samples |
ES2898200T3 (en) | 2014-09-26 | 2022-03-04 | Abbott Point Of Care Inc | Microfabricated device with microenvironment sensors to assess coagulation in fluid samples |
CN107107056B (en) | 2014-09-26 | 2020-04-14 | 雅培医护站股份有限公司 | Single channel cartridge apparatus for coagulation assays in fluid samples |
CN106999932A (en) | 2014-09-26 | 2017-08-01 | 雅培医护站股份有限公司 | The cartridge device with fluid knot determined for the condensation in fluid sample |
CN104714036B (en) * | 2015-04-01 | 2016-06-01 | 成都协和生物技术有限责任公司 | The preparation method of Antithrombin III determination of activity test kit |
CN105203479A (en) * | 2015-09-21 | 2015-12-30 | 山东万邦赛诺康生化制药股份有限公司 | Method for detecting potency of heparin or heparin with low molecular weight through a coagulometer |
EP3388838B1 (en) * | 2016-01-29 | 2022-02-16 | Sony Group Corporation | Blood coagulation analysis |
JP2020504290A (en) * | 2016-10-20 | 2020-02-06 | ユニバーサル バイオセンサーズ ピーティーワイ リミテッドUniversal Biosensors Pty Limited | Biohazard-free solutions and methods for test analyzers |
CN115032164B (en) * | 2022-08-10 | 2022-12-06 | 山东省食品药品检验研究院 | Method for detecting whether heparin sodium contains blood coagulation factor Xa direct inhibitor |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5093237A (en) | 1988-03-03 | 1992-03-03 | Nippon Shoji Kabushiki Kaisha | Method and reagent for determining the biological activity of antithrombin iii by measuring coagulation time |
CA2070813C (en) | 1990-11-05 | 1996-10-29 | Hendrik Coenraad Hemker | A method to determine the concentration of anticoagulants |
US5308756A (en) * | 1991-11-20 | 1994-05-03 | Baxter Diagnostics Inc. | Protein S chromogenic assay |
CA2143842A1 (en) * | 1992-09-04 | 1994-03-17 | Thomas Exner | Apparatus and method for detecting coagulation/lysis of liquids |
KR100305306B1 (en) * | 1993-02-17 | 2001-11-22 | 존 펑크하우저 | Dry chemical cascade immunoassay and affinity analysis |
US5762770A (en) * | 1994-02-21 | 1998-06-09 | Boehringer Mannheim Corporation | Electrochemical biosensor test strip |
SI9520044B (en) * | 1994-04-26 | 2004-08-31 | Aventis Pharmaceuticals Inc. | FACTOR Xa INHIBITORS |
NL1006429C2 (en) * | 1997-06-27 | 1998-12-29 | Univ Maastricht | Method for determining the heparin content. |
US5997817A (en) * | 1997-12-05 | 1999-12-07 | Roche Diagnostics Corporation | Electrochemical biosensor test strip |
AU5062100A (en) * | 1999-06-14 | 2001-01-02 | Novo Nordisk A/S | Fviia/tf activity inhibiting compounds |
WO2001044493A2 (en) * | 1999-12-15 | 2001-06-21 | Pentapharm Ag | Hematological assay and reagent |
US6438498B1 (en) * | 2000-02-10 | 2002-08-20 | I-Stat Corporation | System, method and computer implemented process for assaying coagulation in fluid samples |
WO2001063271A1 (en) * | 2000-02-21 | 2001-08-30 | F. Hoffmann-La Roche Ag | Electrochemical sensor for determining blood clotting, corresponding system for measuring blood clotting and method for determining blood clotting |
US20030146113A1 (en) * | 2000-02-21 | 2003-08-07 | Volker Unkrig | Electrochemical sensor for determining blood clotting, corresponding system for measuring blood clotting and method for determining blood clotting |
US7166208B2 (en) * | 2004-03-03 | 2007-01-23 | Stephen Eliot Zweig | Apoenzyme reactivation electrochemical detection method and assay |
US6680177B2 (en) * | 2001-12-07 | 2004-01-20 | Cardiovascular Diagnostics, Inc. | Low molecular weight heparin assay, system and reagent therefor |
US7579000B2 (en) * | 2002-05-01 | 2009-08-25 | Bayer Schering Pharma Ag | Tissue factor targeted antibodies as anticoagulants |
US7727736B2 (en) * | 2003-09-22 | 2010-06-01 | The University Of North Carolina At Chapel Hill | Soluble phospholipids for use in clotting factor assays |
-
2006
- 2006-10-31 EP EP06123234A patent/EP1918718A1/en not_active Ceased
-
2007
- 2007-10-27 ES ES07819390.1T patent/ES2444011T3/en active Active
- 2007-10-27 WO PCT/EP2007/009347 patent/WO2008052718A1/en active Application Filing
- 2007-10-27 JP JP2009533745A patent/JP5395669B2/en active Active
- 2007-10-27 CN CN2007800408199A patent/CN101535498B/en active Active
- 2007-10-27 CA CA2667957A patent/CA2667957C/en not_active Expired - Fee Related
- 2007-10-27 EP EP07819390.1A patent/EP2079849B1/en active Active
-
2009
- 2009-04-29 US US12/432,490 patent/US8636894B2/en active Active
-
2010
- 2010-03-15 HK HK10102678.3A patent/HK1137783A1/en not_active IP Right Cessation
-
2013
- 2013-12-20 US US14/136,769 patent/US9594042B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
US20090236238A1 (en) | 2009-09-24 |
CN101535498A (en) | 2009-09-16 |
JP2010508499A (en) | 2010-03-18 |
US8636894B2 (en) | 2014-01-28 |
CA2667957C (en) | 2013-03-05 |
US9594042B2 (en) | 2017-03-14 |
EP1918718A1 (en) | 2008-05-07 |
US20140106383A1 (en) | 2014-04-17 |
EP2079849A1 (en) | 2009-07-22 |
JP5395669B2 (en) | 2014-01-22 |
CN101535498B (en) | 2012-11-14 |
ES2444011T3 (en) | 2014-02-21 |
WO2008052718A1 (en) | 2008-05-08 |
EP2079849B1 (en) | 2013-11-20 |
HK1137783A1 (en) | 2010-08-06 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKLA | Lapsed |
Effective date: 20191028 |